Aryl and hetero-aryl phosphorous compounds including phosphonates, phosphinites and phosphine oxides are valuable intermediates in organic synthesis and find applications in organic synthesis, polymers, medicinal chemistry and nucleic acid chemistry. Several methods are known in the art for the synthesis of aryl, hetero-aryl phosphorous compounds. Michaelis-Arbuzov reaction (also called the Arbuzov reaction) which is frequently used involves a reaction of trialkyl phosphite and an alkyl halide to form a phosphonate, however the methodology for the synthesis of aryl phosphonates was limited due to poor reactivity of aryl halides until Hirao developed palladium catalyzed coupling of arylhalides with hydrogen-phosphonates. Several other metal catalyzed processes were developed for the C—P bond forming reactions for synthesis of aryl phosphonates.
An article titled “Copper-Catalyzed C—P Bond Construction via Direct Coupling of Phenylboronic Acids with H-Phosphonate Diesters” by Rongqiang Zhuang, Jian Xu et. al in Organic Letters 2011 Vol. 13, No. 8 pg. nos 2110-2113 discloses copper-catalyzed reaction of H-phosphonate diesters to boronic acids under the copper catalyst system Cu2O/1,10-phenanthroline to form aryl phosphonates.
Recently, oxidative phosphorylation of arylboronic acids catalyzed by palladium or copper has been revealed.
The utilization of aryl triflates as substrates was found attractive in organic reactions, since the phenol derivatives are readily available and may be used as a directing group for the introduction of other functional groups on the aromatic ring, thus allowing access to wider substrate scope.
An article titled “Nickel-catalyzed Arbuzov reactions of aryl triflates with triethyl phosphite” by Guoqiang Yang, Chaoren Shen et. al in Tetrahedron Letters 52 (2011) 5032-5035 relate to nickel-catalyzed phosphorylation of aryl triflates with triethyl phosphite, in which KBr as an additive promoted the SN2 catalytic step. The reaction is carried out at a temperature in the range of 185-190° C. for about 20 hours.
While the processes in the art generate the desired aryl phosphonates, however, the reactions include reactants which are costly such as expensive phosphorous containing ligands, require the use of organic or inorganic bases, transition metal catalysts and the reactions typically proceed at high temperature and involve longer time.
Arynes are known as extremely useful reactive intermediate in organic synthesis. As it is kinetically unstable, highly strained molecule it can readily undergo addition reactions. Key consideration in the development of aryne chemistry is the generation of the reactive intermediate and its precursor. Various methods are known for the production of arynes. A mild and effective method to form a aryne intermediate is to use fluoride induced ortho elimination of o-(trimethylsilyl)aryl triflates which can be easily prepared with various substituents on the arene ring. Thesis titled ‘Development of Versatile Strategies for Aryne Annulation, Applications In Methodology And Natural Product Total Synthesis’ 2010 by Kevin McCormack Allan, also mentions the generation of benzyne by a method developed by Kobayashi and co-workers which involves fluoride induced ortho elimination of o-(trimethylsilyl)aryl triflates.
However, the preparation of aryl phosphorous compounds via arynes at milder conditions is not known.
With a view to develop a facile process for the synthesis of aryl phosphorous compounds, which is convenient, inexpensive and ameliorates the drawbacks of the prior art processes, the present inventors piloted their scope of invention in the synthesis of aryl phosphorous compounds via generation of aryne intermediate from silyl triflates.